TWI679031B - Protection of contact lenses from microbial contamination caused by handling - Google Patents

Abstract

The invention relates to a sealed contact lens package, which comprises a sterile unworn contact lens and a contact lens packaging solution containing epsilon polyionine (εPLL). The εPLL protects the contact lens from microbial contamination caused by operating the lens when it is removed from the lens package.

Description

Protect contact lenses from microbial contamination caused by handling

The field of the invention is contact lens packaging.

Microbiological contamination of contact lenses is a serious public health problem because it is related to eye infiltration, infection, and microbial keratitis. Studies have confirmed that lens manipulation greatly increases the incidence of microbial contamination of lenses (see, eg, Szczotka-Flynn et al., Eye Contact Lens (2010) 36 (2): 116-29). As the contact lenses are not stored in the original packaging solution and used again after use, the risk of contamination is particularly high for daily disposable contact lens wearers (Boost et al., Optom Vis Sci (2011) 88 (12: 1409- 13).

The ε-polylysine is a homopolymer of about 25 to 35 L-lysine residues, in which the ε-amino group of L-lysine is linked to a carboxyl group. It is a natural polymer produced by Streptomyces species. It has broad-spectrum antimicrobial activity and has been widely used as a food preservative in Japan and as an additive in various consumer products. The use of ε-polylysine in contact lens care solutions has been described (see, for example, US Patent No. 6,187,264 and US Patent Publication No. 2005/0074467). Antimicrobial hydrogels made from ε-poly-L-lysine-graft-methacrylamide have been reported (Zhou et al., Biomaterials 32 (2011) 2704-2712).

Other background publications include U.S. Patent Application No. 14 / 109,976, U.S. Patent Publication No. 2012/0074352, U.S. Patent Publication No. 2011/0071091, U.S. Patent Publication No. 2005/0074467, U.S. Patent Publication No. 2004/0135967, U.S. Patent No. 4,168,112, U.S. Patent No. 7,282,214, U.S. Patent No. 7,402,318, European Patent No. 1328303B1, and PCT Publication No. WO94 / 13774.

The present invention provides a sealed contact lens package, which includes a sterile unworn contact lens and a contact lens packaging solution. The contact lens packaging solution includes epsilon polyamic acid (εPLL), wherein the unworn contact lens exhibits at least one Reduced microbial contamination, which was determined by testing in which Pseudomonas aeruginosa (PA) introduced into the lens during removal from the contact lens packaging solution was the same as the package but without the εPLL The contact lens packaging solution was compared with a control contact lens. In one aspect of the present invention, in this test, in vitro bioactivity analysis, when tested after incubating at 10 ⁴ CFU PA for 24 hours, compared with the control contact lens, the PA of the non-wearing contact lens is The log kill is less than two. In another aspect of the present invention, the contact lens package includes (a) a plastic basic member containing a chamber containing a sterile unworn contact lens and a contact lens packaging solution containing epsilon polyionine (εPLL); And (b) a resealable lid forming a liquid-tight seal with the plastic base member.

I confirm that initially removing contact lenses from their original sterile packaging can cause significant microbial contamination of the lenses, even when operating immediately after washing hands. I have found that the addition of epsilon poly (amino acid) (epsilon PLL) to a contact lens packaging solution can reduce or completely eliminate this lens operation pollution. Disclosed herein is a sealed contact lens package that includes a sterile unworn contact lens and a contact lens packaging solution, the latter containing epsilon poly (amino acid) (εPLL), whose content can effectively reduce or completely eliminate its introduction during self-package removal Microbial contamination of lenses. As used herein, "unworn" means that the contact lens has never been placed on the eye and is "sealed" It means having water-tight sealability.

With the help of the present invention, a sealed contact lens package is provided, which comprises a sterile unworn contact lens and a contact lens packaging solution containing epsilon polyionine (εPLL). Unworn contact lenses exhibit reduced contamination of at least one microorganism. This reduction in contamination can be determined by testing in which Pseudomonas aeruginosa (PA) introduced into the lens during removal of the contact lens packaging solution is compared to a control contact lens encapsulated in the same contact lens packaging solution without the epsilon PLL. In the present invention, at least one microorganism may include (comprise) or include (include) Pseudomonas aeruginosa and / or Staphylococcus aureus (composition), and / or the at least one Microorganisms are microorganisms found in microbial keratitis and / or at least one microorganism that at least partially or completely causes eye infiltration and / or infection.

The contact lens sealed in the contact lens package of the present invention may be made of any contact lens material, including (but not limited to) conventional hydrogels and silicone hydrogels. As used herein, "conventional hydrogel" refers to a polymer formed by combining one or more hydrophilic monomers (such as 2-hydroxyethyl methacrylate (HEMA) or vinyl alcohol) with other monomers as appropriate And materials that do not contain siloxane (that is, a molecule containing at least one Si-O group). Examples of conventional hydrogels include etafilcon A, nelfilcon A, ocufilcon B, ocufilcon D, omafilcon A, omafilcon D, and polymacon. Polysiloxane hydrogel materials are generally formed by polymerizing one or more monomers or prepolymers containing at least one Si-O group with one or more hydrophilic monomers. Examples of polysiloxane hydrogels include balafilcon A, comfilcon A, enfilcon A, somofilcon A, narafilcon A, narafilcon B, lotrafilcon A, stenfilcon A, and senofilcon A. In a particular example, the sealed contact lens package includes a sterile unworn silicone hydrogel contact lens. In a specific example, the silicone hydrogel contact lens is non-ionic, meaning that it does not contain an anionic group that is bound to a cationic amine group present in the epsilon PLL via an ionic interaction. In another specific example, the silicone hydrogel contact lens is made of a material selected from comfilcon A or stenfilcon A. In another In one example, the sealed contact lens package includes an unworn conventional hydrogel contact lens made of a material selected from the group consisting of ocufilcon B, ocufilcon D, or omafilcon A.

The contact lens sealed in the contact lens package of the present invention can be any lens wearing modality. The lens wearing mode refers to how many days and nights the lens can be continuously worn without being removed. In one example, the contact lens sealed in the contact lens package of the present invention is a daily disposable lens. Daily disposable lenses are indicated for single use, worn continuously for up to about 12 or 16 hours, and should be discarded after a single use. In another example, the contact lens sealed in the contact lens package of the present invention is a day-wear lens. Day-wear lenses are worn during wakefulness, usually for up to about 12 to 16 hours, and removed before bedtime. Day-wear lenses are usually stored in contact lens cases, which contain contact lens care solutions for cleaning and disinfecting lenses during periods of non-use. Day-wear lenses are usually discarded after a maximum of 30 days. In another example, the contact lens is a long-wearing contact lens. Long-wearing contact lenses are typically worn continuously for up to 6, 14 or 30 days and nights.

The packaging solution sealed within the contact lens package of the present invention may be any contact lens compatible solution containing an effective amount of epsilon PLL. In one example, the encapsulation solution comprises (consisting of or consists essentially of) a buffering agent and / or a tonicity agent and an aqueous solution (composition) of the epsilon PLL. In another example, the encapsulation solution contains other formulations, such as one or more other antimicrobial and / or comfort agents and / or hydrophilic polymers and / or surfactants and / or other additives that prevent the lens from sticking to the package . The encapsulation solution may have a pH ranging from about 6.8 or 7.0 to about 7.8 or 8.0. In one example, the encapsulation solution comprises a phosphate buffer or a borate buffer. In another example, the encapsulation solution comprises a tonicity agent selected from sodium chloride or sorbitol, and its content is to maintain the osmotic pressure at about 200 to 400 mOsm / kg, and usually about 270 mOsm / kg to about 310 mOsm / kg Within range. In the present invention, references to "example", "an example", "one example" or similar phrases are intended to introduce one of contact lens packaging, unworn contact lenses or packaging solutions. Or multiple features, depending on the context (depending on the context), which may be the same as the previously described or later examples (ie, features) Any combination of them, unless a particular combination of features is mutually exclusive or if the context indicates otherwise.

An effective amount of εPLL is an amount that reduces microbial contamination introduced to the lens during removal from a contact lens package (eg, compared to the absence of εPLL). The ability of εPLL to reduce the microbial contamination introduced to a lens during self-package removal can be demonstrated using methods substantially as described in Example 1 or Example 2 below. Example 1 demonstrates that the inclusion of εPLL in a contact lens packaging solution can significantly reduce contact lens microbial contamination caused by microorganisms on normal non-pathogenic skin. Example 2 demonstrates that including εPLL in a contact lens packaging solution can also significantly reduce contact lens microbial contamination caused by Pseudomonas aeruginosa (PA), one of the most common pathogens associated with microbial keratitis. In a particular example, compared to a control contact lens in the same package containing a contact lens packaging solution that does not contain εPLL but is otherwise identical, the unworn contact lens exhibits PA introduced to the lens during removal from the packaging solution Contamination reduction was determined using a lens manipulation analysis as described or substantially as described in Example 2. In various examples, the epsilon PLL content of the packaging solution is at least 5 ppm, 10 ppm, 25 ppm, 50 ppm, 100 ppm, 150 ppm, 200 ppm, 250 ppm, or 500 ppm. In a specific example, the packaging solution contains 10 to 50 ppm εPLL, 25 to 75 ppm εPLL, 50 to 150 ppm εPLL, or 100 to 500 ppm εPLL. The concentration of εPLL in the packaging solution was determined before it came into contact with the unweared contact lens.

The epsilon PLL is commercially available and is generally available as a homopolymer of about 25 to about 35 lysine (LYS) residues (CAS No. 28211-04-3). All parts of natural εPLL homopolymers can be used. Alternatively, a selected portion of the epsilon PLL (e.g., a homopolymer of 30 to 35 LYS residues) can be used, with the remainder removed and not used in this option. As an alternative to natural epsilon PLLs, epsilon PLLs for encapsulation solutions are available from synthetic peptide methods.

In some examples, as measured using in vitro bioactivity analysis substantially as described in Example 4 below, when tested after incubation at 10 ⁴ CFU (colony forming unit) PA for 24 hours, it is invisible compared to control contact lenses The amount of εPLL contained in the lens packaging solution resulted in a PA log kill of less than two. In this example, the contact lens package is still effective against microbial contamination introduced by operating the lens during the original packaging fluid removal of the lens, and is therefore particularly suitable for daily disposable contact lenses.

I confirmed in Example 2 below that after removing the contact lens packaging without wearing, the remaining packaging solution can be protected against microbial contamination at ambient temperature for up to 16 hours when covered with the original blister foil. Therefore, the contact lens packaging described herein can provide protection against microbial contamination caused by the lens wearer who does not use the lens daily as required to keep the worn lenses in their original packaging and the remaining packaging solution overnight for the next day Caused by wearing. Therefore, in one example, the contact lens package includes a plastic base member that includes a chamber that is structurally designed to receive the contact lens and the packaging solution, and a flange region that extends outwardly around the chamber. A removable foil is attached to this flange area to provide a sealed contact lens package. These contact lens packages (often referred to as "blister packs") are well known in the art (see, for example, U.S. Patent No. 7,426,993). In other examples, the contact lens package includes contact lenses that are indicated to be worn during the day for at least 2 days, wherein the package is structured to allow resealing after the initial opening for subsequent placement of the lenses for storage overnight after wearing. For example, a contact lens package may include a plastic base member and a resealable lid that includes a chamber that is structurally designed to contain the contact lens and the packaging solution. As used herein, a "reclosable lid" is a lid that is structurally designed to form a liquid-tight or spill-proof seal with the base member after opening the contact lens package. For example, the plastic base member may include a plurality of threads that engage a set of compatible threads on a cap serving as a resealable cap. Such structures are commonly used in contact lens care cases (see, e.g., U.S. Patent No. 3,977,517). Therefore, the advantage of the contact lens packaging disclosed herein is that it can play a dual role, namely as a contact lens package for sterile unworn contact lenses and a contact lens carrying case for subsequent worn lenses.

It should be understood that conventional manufacturing methods can be used to make the sealed contact lens package of any of the examples described above. Therefore, one aspect of the present invention is a method for manufacturing a contact lens package, which includes the following steps: dissolving an unworn contact lens and a contact lens package containing εPLL The liquid is placed in the tank, the lid is placed on the tank, and the lid is sealed on the tank. Generally, the container is designed to receive a single pair of contact lenses and an amount of packaging solution sufficient to completely cover the contact lenses, typically about 0.5 to 1.5 ml. The container can be made of any suitable material, such as glass or plastic. In one example, the receptacle includes a plastic base member that includes a cavity that is structurally designed to receive contact lenses and a packaging solution, and a flange region that extends outwardly around the cavity, and the lid includes an attachment to the projection. Edge area to provide a removable foil that seals the contact lens package. The removable foil can be sealed by any conventional means such as heat sealing or gluing. In another example, the receptacle is in the form of a plastic base member containing a plurality of threads, and the lid includes a plastic lid that includes a set of compatible threads that can be resealable with the base member. member. It should be understood that other types of packaging liquids can also be used to provide resealable packaging. For example, a contact lens package may include a plastic cover that includes a component that engages with a compatible feature of the dissolution tank to form an interference fit. The method of manufacturing a sealed contact lens package may additionally include sterilizing the unworn contact lens package by treating the sealed contact lens package with high pressure steam.

Details of contact lenses or lenses, solution components, formulations, and all other details as described in U.S. Patent Application No. 14 / 109,976, entitled "Antimicrobial Ophthalmic Devices", filed on December 18, 2013 The references are incorporated herein and form a part of this application.

The following examples illustrate certain aspects and advantages of the present invention, which should not be construed as being limited thereto.

Example 1: Pollution of commercially available contact lenses after operation with washed hands.

Commercially available balafilcon A contact lenses in original blister packs were used in this lens manipulation study. Five individuals washed their hands with soap and water and dried them with paper towels. The researchers used gloved hands to aseptically open the foil lids of each blister. Each body is removed from the lens, and the lens is gently rubbed with the same hand as used to close the faucet for about 5 seconds. Each rubbed lens was then placed in a separate sterile 2 ml microcentrifuge (Eppendorf ^™ ) tube with 1 mL PBS-T and capped. As used herein, PBS refers to phosphate buffered saline, 0.78% by weight NaCl, 0.05% by weight sodium dihydrogen phosphate, and 0.36% by weight disodium hydrogen phosphate, pH 7.5. PBS-T refers to PBS with 0.05% polysorbate 80.

In order to extract any bacteria from the manipulative lens, the tubes were ultrasonically treated for three 30-second cycles, and each cycle was shaken and mixed for 10 seconds. After the final ultrasonic treatment, the tubes were mixed with a multi-tube oscillating mixer at 1000 rpm for 10 minutes. The entire volume of extract from each tube was inoculated onto a blood agar plate, allowed to dry in a biochemical ventilated kitchen, and incubated at 37 ° C for 48 to 72 hours. Bacteria were counted and recorded as CFU / lens. Biotyper was used to identify each bacterium with a unique phenotype.

All five balafilcon A contact lenses are contaminated with detectable levels of common skin bacteria (staphylococcus epidermidis and staphylococcus vogelii). The contamination range is 115 to 6500 CFU / lens. No lens is sterile. Although identified bacteria are not common in microbial keratitis, they cause disease in immunocompromised patients.

In order to determine whether the εPLL in the contact lens packaging solution will immediately produce protection against the microorganisms deposited during the removal of the lens from the blister package, use individual packaging in a contact lens blister package containing PBS or PBS and a 500ppm εPLL packaging solution. Ocufilcon D, comfilcon A, and omafilcon A contact lenses with foil lids sealed and treated with high-pressure steam were used to repeat the above lens operation study. All three lenses confirmed that when εPLL was present in the packaging solution, the bioburden decreased significantly and the average logarithmic kill was as follows: ocufilcon D-2.4, comfilcon A-1.4 and omafilcon A-2.2.

Finally, I repeated the above lens manipulation study to compare the contamination levels of ocufilcon D contact lenses removed from high-pressure steam-treated sealed packages with or without 500 ppm εPLL PBS packaging solution. We also measured the level of microbial contamination of the ocufilcon D contact lenses removed from its high-pressure steam-treated sealed packaging containing PBS packaging solution. Aseptically remove the lens from its packaging using sterile forceps and place the lens in a well of a 24-well plate containing 1 ml of Optifree ^™ or AQuify ^™ contact lens solution. Lenses exposed to ClearCare ^(TM) brand contact lens solutions were placed in lens holders provided by the manufacturer. After soaking overnight, the lenses (5 lenses of each lens solution) were removed from the care solution using the above-mentioned hand washing operation protocol, and extracted as described above. As expected, ClearCare ^™ contact lens solutions without any antimicrobials do not provide protection against handling contamination. However, unexpectedly, neither Optifree ^™ and AQuify ^™ brand contact lens care solutions, both containing active antimicrobials, had any significant effect on bioburden. Only the solution containing εPLL in the blister resulted in a statistically significant decrease in the bacterial count (p = 0.00002). The results are shown in Table 1.

These experiments show that manipulation is an important source of microbial contamination of conventional hydrogels and silicone hydrogel contact lenses. εPLL protects against environmentally-derived bacteria deposited on the lens by lens manipulation. The retention of εPLL in the encapsulation fluid significantly reduces the bioburden caused by the operation.

Example 2: Analysis of lens operation-contact lenses contaminated with pathogens commonly found in microbial keratitis

Using an improvement of the method described in Nomachi et al., Eye & Contact Lens (2013) 39: 234-238, the autoclave treatment of PBS-encapsulated solutions with or without epsilon PLL (10, 25, 100, or 500 ppm) was evaluated. Bacterial adhesion on the surface of comfilcon A lens removed from the blister pack. Briefly, bacterial adhesion on the surface of comfilcon A contact lenses was evaluated using stock solutions of Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) substantially prepared as described in Example 3 below. Put sterile surgical gloves on both hands aseptically. After opening the seal of the comfilcon A package, immerse the thumb and index finger of the gloved hand in a bacterial suspension (approximately 10 ³ CFU / ml in PBS) and use it to remove the lens from the package. Test four lenses of various packaging solutions. Each lens was placed in a microcentrifuge tube with 1 mL of PBS-T, ultrasonically treated for 1.5 minutes, and mixed by shaking at 1000 rpm for 10 minutes. All volumes of the extract were inoculated onto petri dishes with trypsin casein soy agar (TSA) and grown in an incubator at 37 ° C for two days.

Table 2 below shows the average CFU / lens on contact lenses removed from different packaging solutions (n = 4).

As described above, after removing the contact lens with the index finger and thumb contaminated with PA, the blister package and the remaining packaging solution are covered with the original blister foil at ambient temperature. After 16 hours, all volumes of the remaining packaging solution (~ 1 mL) were inoculated onto petri dishes with TSA and grown in an incubator at 37 ° C for 2 days. The packaging solution without any additional ePL has an average value of 331 CFU / lens. The ePL-containing encapsulation solution did not exhibit microbial growth, that is, all had 0 CFU / lens.

Example 3: Preparation of a bacterial suspension

Cultures were prepared on a rotary shaker at 37 ° C in 50 mL trypsin casein soy broth (TSB) by growing individual colonies of each bacterial species shown in Table 3 below. 1 mL of each culture was centrifuged and the bacterial pellet was resuspended in 1.0 mL of the diluent shown in Table 3. For each bacterial species, a suspension of about 10 ⁸ CFU / mL was prepared by diluting the bacterial suspension to the optical density shown in Table 3. Each suspension was further diluted for use in the operational analysis described in Example 2 or in vitro biological activity analysis described in Example 4.

Example 4: Analysis of in vitro biological activity

The contact lens was removed from its packaging solution and rinsed in 2.5 ml of sterile PBS for a few seconds to remove the residual packaging solution. The rinsed lenses were then transferred to individual wells of a 24-well plate containing 1.0 mL 10 ⁴ CFU PA. The plate was incubated at 37 ° C for 24 hours with gentle shaking. The lenses were removed from the wells and transferred to the wells of a 12-well plate containing 2.5 mL of sterile PBS. Vortex the plate gently for about 30 seconds. Repeat this step once for each lens.

Each cleaned lens was placed in a microcentrifuge tube containing 1 mL of Dey-Engley (DE) neutralization medium, and the adherent bacteria were removed by a combination of ultrasonic treatment for about 2 minutes and shaking and mixing for about 10 minutes. Each of the recovered cell suspensions was serially diluted with a DE neutralization medium, and the appropriate dilution was seeded on TSA. The plates were incubated at 37 ° C overnight and CFU was counted.

The CFU of each plate was multiplied by the dilution factor (DF) and the inoculation dilution factor (PDF). The total CFU recovered for a given sample is then converted to a logarithm of 10. In order to calculate the logarithmic killing of contact lenses (ie, "test lenses") packaged in a packaging solution containing εPLL, subtract the logarithm of CFU / lens of the test lens from the logarithm of the CFU / lens of the control lens. Identical and packaged in the same packaging and contact lens packaging solution, but the packaging solution does not contain εPLL. For example, if the average logarithmic value of the antimicrobial lens is 1.05, and in other aspects The average logarithmic value of the same control lens without active antimicrobial agent is 5.52, and the logarithmic killing system is 5.52-1.05 = 4.47.

Although the disclosure herein refers to certain illustrative examples, it should be understood that these examples are presented by way of example and not by way of limitation. Although illustrative examples are discussed, the foregoing detailed description is intended to be deemed to cover all modifications, alternatives, and equivalents of these examples, as they may fall within the spirit and scope of the present invention as defined by other disclosures .

Many publications and patents have been cited above. Each of the publications and patents cited are incorporated herein by reference.

The invention includes the following aspects / embodiments / features in any order and / or in any combination:

What is claimed is: 1. A sealed contact lens package comprising a sterile unworn contact lens and a contact lens packaging solution containing epsilon poly (amino acid) (epsilon), wherein it is compared with a contact lens packaging solution encapsulated in substantially the same but without epsilon PLL Compared to contact lenses, the unworn contact lenses exhibit reduced contamination of Pseudomonas aeruginosa (PA) introduced into the lens during removal from the contact lens packaging solution.

2. A sealed contact lens package comprising a sterile unworn contact lens and a contact lens packaging solution containing epsilon polyionine (εPLL), wherein the unworn contact lens exhibits reduced contamination of at least one microorganism, wherein The reduction in contamination was determined by testing in which Pseudomonas aeruginosa (PA) introduced into the lens during removal from the contact lens packaging solution was used as a control contact lens encapsulated in the same contact lens packaging solution without the εPLL Compare.

3. The packaging of any of the foregoing or subsequent embodiments / features / morphologies, wherein, in this test, in vitro bioactivity analysis is used to test the contact lenses with the control when tested after incubation at 10 ⁴ CFU PA for 24 hours. In comparison, the PA logarithmic kill of the unworn contact lens is less than two.

4. The packaging of any of the foregoing or subsequent embodiments / features / morphologies, wherein, in this test, in vitro bioactivity analysis is used, compared with control contact lenses when tested after 24 hours incubation at 10 ⁴ CFU PA In contrast, the PA logarithmic kill of the unworn contact lens is less than one (but greater than zero logarithmic kill).

5. The packaging of any preceding or subsequent embodiment / feature / form, wherein the contact lens is a silicone hydrogel contact lens.

6. The packaging of any preceding or subsequent embodiment / feature / form, wherein the contact lens is a non-ionic contact lens.

7. The package of any preceding or subsequent embodiment / feature / form, wherein the contact lens is an ion contact lens.

8. The packaging of any preceding or subsequent embodiment / feature / form, wherein the contact lens is a daily disposable contact lens.

9. The packaging of any preceding or subsequent embodiment / feature / form, wherein the contact lens is a daily contact lens.

10. The packaging of any preceding or subsequent embodiment / feature / aspect, wherein the packaging solution comprises 5 ppm to 500 ppm εPLL.

11. The package of any preceding or subsequent embodiment / feature / aspect, wherein the packaging solution comprises 5 ppm to 50 ppm εPLL.

12. A package according to any of the foregoing or subsequent embodiments / features / forms, wherein the contact lens package further comprises (a) a plastic base member including i) a cavity containing unworn contact lenses and a contact lens packaging solution Chamber, and ii) a flange region extending outwardly around the chamber; and (b) a removable foil attached to the flange region.

13. A package according to any of the foregoing or subsequent embodiments / features / forms, wherein the contact lens package further comprises (a) a plastic base member, which includes a chamber containing an unworn contact lens and a contact lens packaging solution; And (b) a resealable lid forming a liquid-tight seal with the plastic base member.

14. A package according to any preceding or subsequent embodiment / feature / form, wherein the plastic base The component includes a plurality of threads that engage a set of compatible threads on the resealable cap.

15. A package according to any preceding or subsequent embodiment / feature / aspect, wherein the at least one microorganism is Pseudomonas aeruginosa.

16. The package of any preceding or subsequent embodiment / feature / aspect, wherein the at least one microorganism is Staphylococcus aureus.

17. A package according to any preceding or subsequent embodiment / feature / aspect, wherein the at least one microorganism is a microorganism found in microbial keratitis.

18. A method for manufacturing a sealed contact lens package, the method comprising placing an unworn contact lens and a contact lens packaging solution containing εPLL in a container structured to receive the contact lens, and sealing the container with a lid, To provide a sealed contact lens package in which the unworn contact lens exhibits introduction to the lens during removal from the contact lens packaging solution compared to a control contact lens encapsulated in a contact lens packaging solution that is substantially the same but without εPLL The contamination of P. aeruginosa (PA) was reduced, and in vitro bioactivity analysis, when tested after incubating at 10 ⁴ CFU PA for 24 hours, compared with the control contact lens, the PA of the un worn contact lens The log kill is less than two.

19. A method of manufacturing a sealed contact lens package, the method comprising placing an unworn contact lens and a contact lens packaging solution containing εPLL in a container structured to receive the contact lens and sealing the container with a lid, wherein The unworn contact lens exhibits a reduction in contamination of at least one microorganism, wherein the reduction in contamination is determined by a test in which Pseudomonas aeruginosa (PA) and encapsulation introduced into the lens during removal from the contact lens packaging solution The control contact lens in the same contact lens packaging solution without the εPLL was compared, and in vitro bioactivity analysis was used, and when tested after incubation at 10 ⁴ CFU PA for 24 hours, compared with the control contact lens, The PA logarithm of unworn contact lenses is less than two.

20. The method of any preceding or subsequent embodiment / feature / form, wherein the contact lens package is any one of the above embodiments (eg, 1 to 17).

21. The method of any preceding or subsequent embodiment / feature / aspect, further comprising sterilizing an unworn contact lens by treating the sealed contact lens package with high pressure steam.

22. A method of manufacturing a sealed contact lens package, the method comprising placing an unworn contact lens and a contact lens packaging solution containing εPLL in a container designed to receive contact lenses and sealing the container with a lid to provide Sealed contact lens package in which the unworn contact lens exhibits a green color introduced to the lens during removal from the contact lens packaging solution compared to a control contact lens encapsulated in a contact lens packaging solution that is substantially the same but without εPLL Contamination of Pseudomonas (PA) is reduced, and wherein the contact lens package includes a resealable lid.

23. A method of manufacturing a sealed contact lens package, the method comprising placing an unworn contact lens and a contact lens packaging solution containing εPLL in a container designed to receive contact lenses and sealing the container with a lid to provide A sealed contact lens package, wherein the unworn contact lens exhibits a reduction in contamination of at least one microorganism, wherein the reduction in contamination is determined by a test in which green pus is introduced into the lens during removal from the contact lens packaging solution The Bacillus (PA) is compared with a control contact lens encapsulated in the same contact lens packaging solution without the epsilon PLL, and wherein the contact lens package includes a resealable lid.

24. The method of any preceding or subsequent embodiment / feature / aspect, wherein the contact lens package is any one of 1-17.

25. The method of any preceding or subsequent embodiment / feature / aspect, further comprising sterilizing an unworn contact lens by treating the sealed contact lens package with high pressure steam.

The invention may include any combination of these various features or embodiments listed above and / or below in sentences and / or paragraphs. Any combination of features disclosed herein is considered part of the invention and is not intended to limit the features that can be combined.

The Applicant specifically incorporated the entire contents of all cited references into the present invention. In addition, when the quantity, concentration, or other values or parameters When a list of upper and lower limits is given, this should be understood as specifically revealing all ranges formed by any pairing of any range upper limit (or better value) with any range lower limit (or better value) , Regardless of whether the scope was revealed separately. Where a numerical range is referenced herein, unless otherwise stated, the range is intended to include the endpoints and all integers and fractions within the range. It is not intended that the scope of the invention be limited to the specific numerical values recited in defining the scope.

Those skilled in the art will know other embodiments of the present invention by considering this specification and the practice of the present invention disclosed herein. It is hoped that this specification and examples will be considered as exemplary only, and the true scope and spirit of the present invention is indicated by the following patent application scope and equivalents.

Claims (11)

A sealed contact lens package comprising a sterile, non-wearing, non-ionic contact lens and a contact lens packaging solution containing 5 ppm to 250 ppm of epsilon polyionine (εPLL), wherein the unworn contact lens is due to the The presence of epsilon PLL in a contact lens packaging solution exhibits at least a reduction in Pseudomonas aeruginosa (PA) contamination; wherein the reduction in pollution is determined by testing and is introduced to the non-wearing lens during removal from the contact lens packaging solution The contact lens lens PA is compared with a control contact lens encapsulated in the same contact lens packaging solution without the εPLL; and wherein the in vitro bioactivity analysis is used to compare with the control contact lens after incubation at 10 ⁴ CFU PA for 24 hours. In contrast, the PA logarithmic kill of the unworn contact lens is less than two. The packaging of claim 1, wherein the contact lens is a silicone hydrogel contact lens. The packaging of claim 1 or 2, wherein the contact lens is a daily disposable contact lens. The package of claim 1 or 2, wherein the sealed contact lens package includes a plastic base member containing a cavity and a flange region extending outwardly around the cavity, and a removable foil attached to the flange region. If the package of claim 1 or 2 includes: a) a plastic base member including a cavity; and b) a resealable lid forming a liquid-tight seal with the plastic base member. The package of claim 5, wherein the plastic base member includes a plurality of threads for engaging a set of compatible threads on the resealable lid. The packaging of claim 1 or 2, wherein the contact lens exhibits reduced contamination of at least one microorganism. The packaging according to claim 7, wherein the at least one microorganism is Pseudomonas aeruginosa . The package of claim 7, wherein the at least one microorganism is Staphylococcus aureus . The package of claim 7, wherein the at least one microorganism is a microorganism found in microbial keratitis. A method for manufacturing a sealed contact lens package according to any one of the preceding claims 1 to 9, the method comprising: placing an unworn, non-ionic contact lens and a contact lens packaging solution containing εPLL of 5 ppm to 250 ppm The structure is designed to receive a contact lens in a container; the container is sealed with a lid to provide a sealed contact lens package; and the sealed contact lens package is sterilized by treating the sealed contact lens package with high pressure steam.